Sprouty1 is a broad mediator of cellular senescence

Genes of the Sprouty family (Spry1-4) restrain signaling by certain receptor tyrosine kinases. Consequently, these genes participate in several developmental processes and function as tumor suppressors in adult life. Despite these important roles, the biology of this family of genes still remains ob...

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Autores: Anerillas, Carlos, Perramon Güell, Aida, Altés, Gisela, Cuesta, Sara, Vaquero, Marta, Olomí, Anna, Rodríguez Barrueco, Ruth, Llobet Navàs, David, Egea, Joaquim, Dolcet, Xavi, Yeramian, Andrée, Encinas, Mario
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/214215
Acceso en línea:https://hdl.handle.net/2445/214215
Access Level:acceso abierto
Palabra clave:Metabolisme cel·lular
Envelliment
Cell metabolism
Aging
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spelling Sprouty1 is a broad mediator of cellular senescenceAnerillas, CarlosPerramon Güell, AidaAltés, GiselaCuesta, SaraVaquero, MartaOlomí, AnnaRodríguez Barrueco, RuthLlobet Navàs, DavidEgea, JoaquimDolcet, XaviYeramian, AndréeEncinas, MarioMetabolisme cel·lularEnvellimentCell metabolismAgingGenes of the Sprouty family (Spry1-4) restrain signaling by certain receptor tyrosine kinases. Consequently, these genes participate in several developmental processes and function as tumor suppressors in adult life. Despite these important roles, the biology of this family of genes still remains obscure. Here we show that Sprouty proteins are general mediators of cellular senescence. Induction of cellular senescence by several triggers in vitro correlates with upregulation of Sprouty protein levels. More importantly, overexpression of Sprouty genes is sufficient to cause premature cellular senescence, via a conserved N-terminal tyrosine (Tyrosine 53 of Sprouty1). Accordingly, fibroblasts from knockin animals lacking that tyrosine escape replicative senescence. In vivo, heterozygous knockin mice display delayed induction of cellular senescence during cutaneous wound healing and upon chemotherapy-induced cellular senescence. Unlike other functions of this family of genes, induction of cellular senescence appears to be independent of activation of the ERK1/2 pathway. Instead, we show that Sprouty proteins induce cellular senescence upstream of the p38 pathway in these in vitro and in vivo paradigms.Springer Science and Business Media LLC2024202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/214215Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41419-024-06689-4Cell Death & Disease, 2024, vol. 15, num. 4https://doi.org/10.1038/s41419-024-06689-4cc by (c) Anerillas, Carlos et al, 2024http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2142152026-05-29T05:05:01Z
dc.title.none.fl_str_mv Sprouty1 is a broad mediator of cellular senescence
title Sprouty1 is a broad mediator of cellular senescence
spellingShingle Sprouty1 is a broad mediator of cellular senescence
Anerillas, Carlos
Metabolisme cel·lular
Envelliment
Cell metabolism
Aging
title_short Sprouty1 is a broad mediator of cellular senescence
title_full Sprouty1 is a broad mediator of cellular senescence
title_fullStr Sprouty1 is a broad mediator of cellular senescence
title_full_unstemmed Sprouty1 is a broad mediator of cellular senescence
title_sort Sprouty1 is a broad mediator of cellular senescence
dc.creator.none.fl_str_mv Anerillas, Carlos
Perramon Güell, Aida
Altés, Gisela
Cuesta, Sara
Vaquero, Marta
Olomí, Anna
Rodríguez Barrueco, Ruth
Llobet Navàs, David
Egea, Joaquim
Dolcet, Xavi
Yeramian, Andrée
Encinas, Mario
author Anerillas, Carlos
author_facet Anerillas, Carlos
Perramon Güell, Aida
Altés, Gisela
Cuesta, Sara
Vaquero, Marta
Olomí, Anna
Rodríguez Barrueco, Ruth
Llobet Navàs, David
Egea, Joaquim
Dolcet, Xavi
Yeramian, Andrée
Encinas, Mario
author_role author
author2 Perramon Güell, Aida
Altés, Gisela
Cuesta, Sara
Vaquero, Marta
Olomí, Anna
Rodríguez Barrueco, Ruth
Llobet Navàs, David
Egea, Joaquim
Dolcet, Xavi
Yeramian, Andrée
Encinas, Mario
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Metabolisme cel·lular
Envelliment
Cell metabolism
Aging
topic Metabolisme cel·lular
Envelliment
Cell metabolism
Aging
description Genes of the Sprouty family (Spry1-4) restrain signaling by certain receptor tyrosine kinases. Consequently, these genes participate in several developmental processes and function as tumor suppressors in adult life. Despite these important roles, the biology of this family of genes still remains obscure. Here we show that Sprouty proteins are general mediators of cellular senescence. Induction of cellular senescence by several triggers in vitro correlates with upregulation of Sprouty protein levels. More importantly, overexpression of Sprouty genes is sufficient to cause premature cellular senescence, via a conserved N-terminal tyrosine (Tyrosine 53 of Sprouty1). Accordingly, fibroblasts from knockin animals lacking that tyrosine escape replicative senescence. In vivo, heterozygous knockin mice display delayed induction of cellular senescence during cutaneous wound healing and upon chemotherapy-induced cellular senescence. Unlike other functions of this family of genes, induction of cellular senescence appears to be independent of activation of the ERK1/2 pathway. Instead, we show that Sprouty proteins induce cellular senescence upstream of the p38 pathway in these in vitro and in vivo paradigms.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/214215
url https://hdl.handle.net/2445/214215
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41419-024-06689-4
Cell Death & Disease, 2024, vol. 15, num. 4
https://doi.org/10.1038/s41419-024-06689-4
dc.rights.none.fl_str_mv cc by (c) Anerillas, Carlos et al, 2024
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Anerillas, Carlos et al, 2024
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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